Cellular regulation of islet hormone secretion by the incretin hormone glucagon-like peptide 1.
Glucagon-like peptide 1 is a gastrointestinally derived hormone with profound effects on nutrient-induced pancreatic hormone release. GLP-1 modulates insulin, glucagon and somatostatin secretion by binding to guanine nucleotide binding protein-coupled receptors resulting in the activation of adenylate cyclase and generation of cyclic adenosine monophosphate (cAMP). In the B-cell, cAMP, via activation of protein kinase A, interacts with a plethora of signal transduction processes including ion channel activity, intracellular Ca2+ handling and exocytosis of the insulin-containing granules. The stimulatory action of GLP-1 on insulin secretion, contrary to that of the currently used hypoglycaemic sulphonylureas, is glucose dependent and requires the presence of normal or elevated concentrations of the sugar. For this reason, GLP-1 attracts much interest as a possible novel principle for the treatment of human type-2 diabetes. Here we review the actions of GLP-1 on islet cell function and attempt to integrate current knowledge into a working model for the control of pancreatic hormone secretion.
Gromada
J
J
Department of Islet Cell Physiology, Novo Nordisk A/S, The Symbion Science Park, Fruebjergvej 3, DK-2100 Copenhagen, Denmark.
Holst
J J
JJ
Rorsman
P
P
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology; D005089:Exocytosis / Q000502:physiology; D005934:Glucagon / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D004763:Glucagon-Like Peptides; D006801:Humans; D007473:Ion Channels / Q000378:metabolism / Q000502:physiology; D007515:Islets of Langerhans / Q000378:metabolism*; D010187:Pancreatic Hormones / Q000378:metabolism*; D010446:Peptide Fragments / Q000502:physiology* / Q000627:therapeutic use; D011498:Protein Precursors / Q000502:physiology* / Q000627:therapeutic use; D018027:Receptors, Glucagon / Q000378:metabolism
C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007473:Ion Channels; D010187:Pancreatic Hormones; D010446:Peptide Fragments; D011498:Protein Precursors; D018027:Receptors, Glucagon; C055453:glucagon-like peptide 1 (7-36)amide; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D002118:Calcium